Our results found that high HOXC6 expression was markedly linked to the advancement of malignant tumors, poor prognosis, and an immunoevasive environment in patients with CRC, with high presence of Tregs, CD8+ T-cells, neutrophils, and macrophages; declined levels of GZMB and PRF1; and elevated levels of PD-L1 and PD-1. Here, HOXC6 is linked to cancer.